The Effects of Histaminergic Agents in the Nucleus Accumbens of Rats in the Elevated Plus-Maze Test of Anxiety

OBJECTIVE The nucleus accumbens (NAc) receive histaminergic neurons from tuberomammillary nuclei. There are reports indicating that central histamine systems are involved in many physiological behavioral processes, including anxiety. The aim of the present study was to assess whether the histaminergic system of the NAc is involved in anxiety-related behaviors. METHODS Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then were placed in a stereotaxic apparatus. In addition, two stainless-steel cannuale were placed 2 mm above the nucleus accumbens shell. Seven days after recovery from surgery, the behavioral testing was started. As a model of anxiety, the elevated plus maze which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used in male Wistar rats. RESULTS Intra-NAc administration of histamine (0.01, 0.1 and 1 µg/rat) increased the percentage of open arm time (%OAT) and open arm entries (%OAE), but not locomotor activity, indicating an anxiolytic response. Furthermore, bilateral microinjections of different doses of the H(1) receptor antagonist pyrilamine (0.001, 0.01, 0.1 and 1 µg/rat) or the H(2) receptor antagonist ranitidine (0.001, 0.01, 0.1 and 1 µg/rat) into the NAc increased %OAT and %OAE, but not locomotor activity. However, both histamine and histamine receptor antagonists showed an anxiolytic-like effect; the antagonists (1 µg/rat) also decreased the histamine response. CONCLUSION The results may indicate a modulatory effect for the H(1) and H(2) histamine receptors of nucleus accumbens in the anxiety behavior of rats.